The production of radioisotopes typically involves irradiating a target fluid (gas or liquid) maintained within a target assembly with an energetic charged particle beam. The energetic charged particle beam may be characterized by one or more parameters such as particles per second, beam current (typically measured in microamps (μA) or milliamps (mA)), particle velocity, beam energy (typically measured in kilo electron volts (KeV) or mega electron volts (MeV)), and beam power (typically measured in watts (W)). The interaction of one of the energetic particles from the particle beam with a target nucleus in the target fluid will, under the appropriate conditions, tend to produce a nuclear reaction that transforms the target nucleus into a different element.
These nuclear reactions may be written as a shorthand expression X(a,b)Y in which X represents the target nuclei, a is the incoming or beam particle, b is the particle emitted by the nuclei, and Y represents the resultant or product nuclei. An example of such an expression is 18O(p,n)18F, which indicates a nuclear reaction in which the oxygen isotope 18O is struck by a proton, which enters the nucleus and causes a neutron to be ejected, resulting in a change in the nuclear structure to the fluorine isotope 18F. Another example of such an expression is 14N(p,α)11C, which indicates that the nitrogen isotope 14N is struck by a proton, which enters the nucleus and causes an α particle to be emitted, resulting in a change in the nuclear structure to the carbon isotope 11C.
The probability of a nuclear reaction occurring is referred to as the cross-section and is a function of the incoming particle energy and differs for each combination of target nuclei, incoming particle, and leaving particle. For the production of a particular radioisotope, type of particle, the beam current, beam energy, target nuclei and target density may be selected to increase the likelihood of the preferred nuclear reaction and the yield of the desired product.
The systems used for generating the energetic charged particle beams, such as cyclotrons, electrostatic accelerators and radiofrequency quadrupoles, are typically expensive (usually more than US$1,000,000) to purchase, expensive to maintain and to operate and require highly skilled technical staff. In some cases, the preferred target material may also be expensive to purchase, such as enriched 18O gas (typically more than US$500 per liter) and enriched 18O water (typically more than US$100 per milliliter). These enriched 18O materials are, however, commonly used target materials for the production of the fluorine isotope 18F. The 18F is, in turn, frequently utilized in the production of radiolabeled materials, such as the radiopharmaceutical 18F-fluorodeoxyglucose (FDG), that may be used in positron emission tomography (PET) for the diagnosis of cancer and other conditions.
As noted above, the cross-section parameter reflects the probability that the desired nuclear reaction will occur. The yield of the desired product can, therefore, be enlarged by increasing the number of incoming energetic particles, i.e., the beam current. Increasing the number of incoming energetic particles, while maintaining the same beam energy, will tend to increase the number of product nuclei generated. The range, or distance travelled through a medium, of a charged particle is a function of the energy of the charged particle and the properties of the medium or media through which it will travel. The range values for a wide range of particles, energies and media are generally known or readily available to those of skill in the art.
There is a phenomenon in fluid targets, particularly gas targets, which tends to reduce the energy deposited in the target material even as the total power applied to the target assembly increases if the beam energy remains substantially constant. This phenomenon is referred to as a density reduction. This phenomenon has been attributed to the interaction between the charged particle beam and the target fluid during which most of the energy transfer results in ionization rather than nuclear reactions. This energy transfer heats the target fluid, causing it to rise and consequently move away from the region of the incoming particle beam.
This phenomenon was first noted in Bame S. J. Jr., Perry J. E. Jr., T(d,n)4He Reaction, Physical Review, Vol. 107, pp. 1616-20, 1957. Robertson et al.'s 1961 article, i.e., Robertson L. P., White B. L., Erdman K. L., Beam Heating Effects in Gas Targets, Review of Scientific Instruments, Vol. 32, p. 1405, 1961, provides a study of beam heating. And, in 1982, Heselius et al. published photographs of the beam interaction in a gas target in Heselius S. J., Lindbolm P., and Solin O., Optical Studies Of The Influence Of An Intense Ion Beam On High-Pressure Gas Targets, Int'l J. of Applied Radiation, Vol. 33, pp. 653-659, 1982, that depicted the extended beam travel as the beam current increased for a fixed energy. Each of the referenced articles is hereby incorporated by reference, in their entirety.
This movement of the target nuclei away from the beam region reduces the number of nuclei in the beam path (density) and hence increases the range of the beam, or in the case of a fixed distance, decreases the proportion of the beam power transferred to the target nuclei. This in turn decreases the number of the nuclear reactions that will occur and reduces the number of product nuclei that are produced.
A factor affecting the density reduction in a gas target is the ability of the target assembly to maintain the gas at a uniform temperature. One approach aims to suppress the convective movement of the heated target gas away from the incident particle beam by configuring the target assembly to provide a target envelope that is closely matched to the configuration of the incoming charged particle beam, thereby forcing substantially all of the target nuclei to remain in the path of the beam. Other approaches include increasing the length of the target and/or increasing the loading pressure to increase the number of target nuclei that will be exposed to the incident particle beam substantially above those values required when little heat is generated in the target assembly. These approaches can compensate to some degree for the pressure differential that will be generated within the target fluid inside the target envelope and the resulting localized density reduction.
An additional factor affecting the process yield is that the incoming charged particle beam tends to lack spatial uniformity with respect to particle distribution. Indeed, a typical distribution of particles within the beam will exhibit a substantially gaussian radial distribution perpendicular to the beam direction. This means that the particle distribution within the beam is biased toward a central portion of the beam and the convective movement of the target gas will tend shift the target nuclei to areas within the target assembly that are exposed to fewer beam particles, thereby tending to decrease production of the desired product isotope(s).
As a result, even closely matching the configuration of the target chamber to the beam shape will generally not fully counteract the heating induced density reduction of the target gas in the higher beam density regions. Further, target assemblies in which the target chamber includes little or no volume that is not within the beam strike region tend to experience much greater pressure increases than targets that include substantial target chamber volume that is not within the beam strike region. In order to accommodate the greater pressure increases experienced within the reduced volume target chamber, the chamber beam windows and chamber walls must be made stronger which, in the case of the chamber beam window, can reduce the percentage of beam energy and/or beam current that can be applied to the target gas.